First Experimental Quantitative Charge Density Studies of Advanced Intermediate of Vitamin D Analogues

• Published in: Molecules (Basel, Switzerland) Vol. 27; no. 6; p. 1757
• Main Authors: Wanat, Monika, Malinska, Maura, Kutner, Andrzej, Woźniak, Krzysztof
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08.03.2022; MDPI
• Subjects: Biological activity; Calciferol; Charge density; Cholecalciferol; Conformation; Crystal structure; Crystallography; Electron density; electrostatic interactions; Electrostatic properties; Hydrogen bonds; Molecular Conformation; Psoriasis; Receptors, Calcitriol; Rings (mathematics); Topology; Vitamin D; Vitamins; vitamin D; electrostatic interactions; electron density
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27061757

Vitamins D are a group of fat-soluble secosteroids which play a regulatory role in the functioning of most cells. Rational design of new vitamin D analogs, of increased therapeutic potency and lowered calcemic side effects, requires high-resolution initial structures and a deep understanding of interactions with the molecular targets. In this paper, using quantum crystallography, we present the first determination of the experimental quantitative charge density of an advanced intermediate of vitamin D analogues as well as a reconstruction of the theoretical electron density of final vitamin D analogues. Application of these methods allows for topological and electrostatic interaction energy analysis. We showed that the A-ring chair conformation has a significant influence on the topological properties of vitamin D compounds. Moreover, the interactions between the CD-ring and side-chain additionally stabilize the crystal structure. These results are supported by our theoretical calculations and previous biological studies.